CA2108183C - Synergistic antimicrobial combination of polyether phosphonates and non-oxidizing biocides - Google Patents
Synergistic antimicrobial combination of polyether phosphonates and non-oxidizing biocides Download PDFInfo
- Publication number
- CA2108183C CA2108183C CA002108183A CA2108183A CA2108183C CA 2108183 C CA2108183 C CA 2108183C CA 002108183 A CA002108183 A CA 002108183A CA 2108183 A CA2108183 A CA 2108183A CA 2108183 C CA2108183 C CA 2108183C
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- CA
- Canada
- Prior art keywords
- hydrogen
- methyl
- dibromo
- average
- polyether
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229920000570 polyether Polymers 0.000 title claims abstract description 43
- 239000004721 Polyphenylene oxide Substances 0.000 title claims abstract description 42
- 230000000845 anti-microbial effect Effects 0.000 title claims abstract description 42
- 230000002195 synergetic effect Effects 0.000 title claims abstract description 42
- 239000003139 biocide Substances 0.000 title claims abstract description 26
- 230000001590 oxidative effect Effects 0.000 title claims abstract description 22
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 title description 9
- 230000012010 growth Effects 0.000 claims abstract description 37
- 230000000813 microbial effect Effects 0.000 claims abstract description 20
- TTZMPOZCBFTTPR-UHFFFAOYSA-N O=P1OCO1 Chemical class O=P1OCO1 TTZMPOZCBFTTPR-UHFFFAOYSA-N 0.000 claims abstract description 13
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 12
- DHVLDKHFGIVEIP-UHFFFAOYSA-N 2-bromo-2-(bromomethyl)pentanedinitrile Chemical compound BrCC(Br)(C#N)CCC#N DHVLDKHFGIVEIP-UHFFFAOYSA-N 0.000 claims abstract description 11
- JWZXKXIUSSIAMR-UHFFFAOYSA-N methylene bis(thiocyanate) Chemical compound N#CSCSC#N JWZXKXIUSSIAMR-UHFFFAOYSA-N 0.000 claims abstract description 10
- UUIVKBHZENILKB-UHFFFAOYSA-N 2,2-dibromo-2-cyanoacetamide Chemical compound NC(=O)C(Br)(Br)C#N UUIVKBHZENILKB-UHFFFAOYSA-N 0.000 claims abstract description 8
- RUPBZQFQVRMKDG-UHFFFAOYSA-M Didecyldimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCC[N+](C)(C)CCCCCCCCCC RUPBZQFQVRMKDG-UHFFFAOYSA-M 0.000 claims abstract description 7
- CGMKPKRNUNDACU-UHFFFAOYSA-N carbamimidoyl(dodecyl)azanium;chloride Chemical compound Cl.CCCCCCCCCCCCN=C(N)N CGMKPKRNUNDACU-UHFFFAOYSA-N 0.000 claims abstract description 7
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
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- 230000015572 biosynthetic process Effects 0.000 claims description 7
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 5
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- 229940100555 2-methyl-4-isothiazolin-3-one Drugs 0.000 abstract description 3
- 229940100484 5-chloro-2-methyl-4-isothiazolin-3-one Drugs 0.000 abstract description 3
- DHNRXBZYEKSXIM-UHFFFAOYSA-N chloromethylisothiazolinone Chemical compound CN1SC(Cl)=CC1=O DHNRXBZYEKSXIM-UHFFFAOYSA-N 0.000 abstract description 3
- BEGLCMHJXHIJLR-UHFFFAOYSA-N methylisothiazolinone Chemical compound CN1SC=CC1=O BEGLCMHJXHIJLR-UHFFFAOYSA-N 0.000 abstract description 3
- FWJHCLIGRLVRIT-UHFFFAOYSA-N 1,3-benzothiazol-2-ylsulfanylmethyl thiocyanate;pentanedial Chemical compound O=CCCCC=O.C1=CC=C2SC(SCSC#N)=NC2=C1 FWJHCLIGRLVRIT-UHFFFAOYSA-N 0.000 abstract 1
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- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
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- RTWNYYOXLSILQN-UHFFFAOYSA-N methanediamine Chemical compound NCN RTWNYYOXLSILQN-UHFFFAOYSA-N 0.000 description 3
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- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
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- CBFCDTFDPHXCNY-UHFFFAOYSA-N octyldodecane Natural products CCCCCCCCCCCCCCCCCCCC CBFCDTFDPHXCNY-UHFFFAOYSA-N 0.000 description 1
- 239000005012 oleoresinous Substances 0.000 description 1
- 235000010292 orthophenyl phenol Nutrition 0.000 description 1
- 230000000590 parasiticidal effect Effects 0.000 description 1
- 239000002297 parasiticide Substances 0.000 description 1
- 229940112041 peripherally acting muscle relaxants other quaternary ammonium compound in atc Drugs 0.000 description 1
- 238000004391 petroleum recovery Methods 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- 238000004537 pulping Methods 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000003134 recirculating effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical class [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Chemical class 0.000 description 1
- 235000017454 sodium diacetate Nutrition 0.000 description 1
- 235000010294 sodium orthophenyl phenol Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 229930188428 trichomycin Natural products 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
- A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
- A01N57/20—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds containing acyclic or cycloaliphatic radicals
Abstract
Synergistic antimicrobial combinations of polyether polyamino methylene phosphonates and one or more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole glutaraldehyde;
potassium dimethyldithiocarbamate;
5-chloro-2-methyl-4-isothiazolin-3-one;
2-methyl-4-isothiazolin-3-one;
tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane;
are useful for inhibiting microbial growth in a variety of aqueous systems.
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole glutaraldehyde;
potassium dimethyldithiocarbamate;
5-chloro-2-methyl-4-isothiazolin-3-one;
2-methyl-4-isothiazolin-3-one;
tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane;
are useful for inhibiting microbial growth in a variety of aqueous systems.
Description
s a . ~~ c, ~
~~.~~.C;:~
s 3776H C-i~~s TTTt.F QF TgE Ijvj~TFNTTIITeT
SYNERGISTIC ANTIMICROBIAL COMBINATION OF POLYETHER
PHOSPHONATES AND NON-OXIDIZING BIOCIDES
BACKGROUND OF THF T~r~~rTTnN
1. Field of the Invention The present invention is concerned with antimicrobial compositions which are useful for inhibiting microbial growth wherever such microbial growth is und~essirable, e.g. , aqueous systems found in a variety of industrial applications, such as papermak~.ng.
.In particular, the present invention is concerned with antimicrobial compositions which comprise a synergistic mixture of two components, One component i~ .J
is a polyether polyamino methylene phosphonate, which has also been found to exhibit excellent calcium . carbonate scale inhibition under the severe .
conditions of high calcite concentration and high pH
which characterize, e.g., a cycled up cooling tower.
Thus, control of unwanted microbial growth in such systems is provided in addition to scale control;
however, the present invention is not limited to such appal i cat i ons .
The other component of the synergistic mixture is a non-oxidizing biocide, which is' one or more members selected from the group consisting essentialiy,of those detailed further herein. All of these non-oxidizing biocides, as well as combinations thereof, are well known in the antimicrobial art.
However, the discovery that .these conventional non-oxidizing biocides could form the basis for synergistic combinations with the polyether phosphonates described herein, was both surprising 2o and unexpected.
As used herein, the phrases, "aritimicrobial" and "inhibiting microbial growth" describe the killing of or destruction of, as well as the inhibition of or control of the growth or propagation of bacteria, fungi (including yeasty and molds) and algae in dormant, immature developing and/or mature stages. A
number of important industries can experience serious ' adverse effects from the activity of such bacteria arid fungi on the raw materials which they employ, on 3o various aspects of their manufacturing activities, or on the finished p.roducts~ which they produce. Such industries include the paint, wood, textile, cosmetic, leather, tobacco, fur, rope, paper, pulp, plastics, fuel, oil, rubber, and machine industries.
3776H _3_ c-.1578 Important applications of the synergistic antimicrobial combination of the present invention include: inhibiting the growth of bacteria and fungi in aqueous paints, adhesives, latex emulsions, and joint cements; preserving wood; preserving cutting oils; controlling slime-producing bacteria~and fungi in pulp and paper mills and cooling waters; as a Spray or dip treatment for textiles and leather to prevent mold growth; as a component of anti-fouling to paints to prevent adherence of fouling organisms;
protecting paint films, especially exterior paint's, from attack by fungi which occurs during weathering of the paint film; protecting processing equipment from slime deposits~during manufacture of cane and beet sugar; preventing microorganism buildup and deposits in air washer or scrubber systems and in industrial fresh water supply systems; controlling microorganism contamination end deposits~in oil field drilling fluids and muds, and in secondary petroleum recovery processes; preventing bacterial and fungal growth~in paper coating processes which might adversely affect the quality of the paper coating;
controlling bacterial and fungal growth and deposits during the manufacture of various specialty boards, e,g,, cardboard and particle board; preventing sag stain discoloration on freshly cut wood of various kinds; controlling bacterial and fungal lgrowth in clay and pigment slurries of various types which are manufactured for later use in paper coating and paint 3p ' manufacturing for example, and which &re susceptible to degradation by microorganisms during storage and transport; as a hard surface disinfectant to prevent growth of bactexia and fungi on walls, floors, etc.;
and in swimming pools to prevent algae growth.
The control of bacteria and fungi in pulp and paper mill water systems which contain aqueous dispersions of gapermaking fibers is especially important. The uncontrolled buildup of slime produced by the accumulation of bacteria and fungi causes offgrade production, decreased production due to breaks and greater cleanup frequency, increased raw material usage, and increased maintenance costs.
The problem of slime deposits has been aggravated by 1o the widespread use of closed white water systems in the paper industry.
Another important area where control of bacterial and fungal growth is vital is an clay and pigment.
slurries. These slurries are of various clays, e.g.
15 kaolin, and pigments, e.g. calcium carbonate and ' titanium dioxide, and are manufactured usually at a location separate from the end use application, in for example, paper coating and paint manufacturing, and aye then stored and held for later transport to 20 the end use location. Because of the high quality standards foi the paper and paint final products in which the slurry is used, it is essential that the clay or pigment slurry have a very low microorganism count or content so that it is usable in the paper a5 coating or paint manufacturing.
Yet another important area for cantrolling microbial growth is cooling systems such as those .
using cycled up recirculating.cooling towers. Such systems maintain a large body of water for a 30 considerable length of time exposed to the atmosphere under canditions which do not include sufficient aeration and exposure to sunlight to provide contxol of microbial, especially bacterial and fungal, 3776H -5- G-1.578 growth. In particular, many cooling towers use fill composed of beads of synthetic polymer or other materials, in order to extend the amount of heat exchange surface area, and this type of construction ~ greatly aggravates the problem of microbiological growth, since it provides an ideal physical environment for the propagation of. troublesome microbes. Unchecked, such microorganisms flourish and produce colonies extensive enough to give rise to to problems of 'biofilm blockage of heat exchange surfaces, as well as clogging of the components of the water transporting apparatus used in operating the cooling system. The synergistic combinations of the present invention providelnot only excellent control of microbial growth in such systems, but also .inhibit the deposition of calcium carbonate scale as well.
The synergistic combination of the present invention has been found especially useful in controlling t',he harmful effects of microorganisms in water or aqueous media. Systems which utilize circulating water or aqueous media become infected with microorganisms and experience substantial impairment of their efficiency when deposits of the microorganisms build up in the system. The deposits, called slimes, coat the walls of tanks arid other vessels, and any machinery or processing equipment which is employed,, and create blockages in pipes and valves. The slime formation promotes corrosion of metal surfaces and facilitates the deterioration of wooden towers.' The slimes also create.discolorations and other imperfections in any products being produced, forcing costly shutdowns. Control of microorganisms in aqueous media is paxticulary 3776H -s- C-1578 important where there are dispersed particles or fines in the aqueous media, e.g.., dispersed cellulosic fibers and dispersed fillers and pigments in papermaking, and dispersed pigments in paint manufacture.
The synergistic antimicrobial combination of the present invention may also be utilized for agricultural and animal health applications, for example in preventing or minimizing the growth of harmful bacteria, yeast, and/or molds on plants, trees, fruit, seeds or soil. The synergistic .
combination may be useful in treating seed to prevent microorganism, particularly fungal attack. The synergistic combination may also be useful in protecting animal dip compositions against the buildup of microorganisms, and for this purpose may be combined with a veterinary animal dip parasiticide and an acceptable carrier.
~~.~~.C;:~
s 3776H C-i~~s TTTt.F QF TgE Ijvj~TFNTTIITeT
SYNERGISTIC ANTIMICROBIAL COMBINATION OF POLYETHER
PHOSPHONATES AND NON-OXIDIZING BIOCIDES
BACKGROUND OF THF T~r~~rTTnN
1. Field of the Invention The present invention is concerned with antimicrobial compositions which are useful for inhibiting microbial growth wherever such microbial growth is und~essirable, e.g. , aqueous systems found in a variety of industrial applications, such as papermak~.ng.
.In particular, the present invention is concerned with antimicrobial compositions which comprise a synergistic mixture of two components, One component i~ .J
is a polyether polyamino methylene phosphonate, which has also been found to exhibit excellent calcium . carbonate scale inhibition under the severe .
conditions of high calcite concentration and high pH
which characterize, e.g., a cycled up cooling tower.
Thus, control of unwanted microbial growth in such systems is provided in addition to scale control;
however, the present invention is not limited to such appal i cat i ons .
The other component of the synergistic mixture is a non-oxidizing biocide, which is' one or more members selected from the group consisting essentialiy,of those detailed further herein. All of these non-oxidizing biocides, as well as combinations thereof, are well known in the antimicrobial art.
However, the discovery that .these conventional non-oxidizing biocides could form the basis for synergistic combinations with the polyether phosphonates described herein, was both surprising 2o and unexpected.
As used herein, the phrases, "aritimicrobial" and "inhibiting microbial growth" describe the killing of or destruction of, as well as the inhibition of or control of the growth or propagation of bacteria, fungi (including yeasty and molds) and algae in dormant, immature developing and/or mature stages. A
number of important industries can experience serious ' adverse effects from the activity of such bacteria arid fungi on the raw materials which they employ, on 3o various aspects of their manufacturing activities, or on the finished p.roducts~ which they produce. Such industries include the paint, wood, textile, cosmetic, leather, tobacco, fur, rope, paper, pulp, plastics, fuel, oil, rubber, and machine industries.
3776H _3_ c-.1578 Important applications of the synergistic antimicrobial combination of the present invention include: inhibiting the growth of bacteria and fungi in aqueous paints, adhesives, latex emulsions, and joint cements; preserving wood; preserving cutting oils; controlling slime-producing bacteria~and fungi in pulp and paper mills and cooling waters; as a Spray or dip treatment for textiles and leather to prevent mold growth; as a component of anti-fouling to paints to prevent adherence of fouling organisms;
protecting paint films, especially exterior paint's, from attack by fungi which occurs during weathering of the paint film; protecting processing equipment from slime deposits~during manufacture of cane and beet sugar; preventing microorganism buildup and deposits in air washer or scrubber systems and in industrial fresh water supply systems; controlling microorganism contamination end deposits~in oil field drilling fluids and muds, and in secondary petroleum recovery processes; preventing bacterial and fungal growth~in paper coating processes which might adversely affect the quality of the paper coating;
controlling bacterial and fungal growth and deposits during the manufacture of various specialty boards, e,g,, cardboard and particle board; preventing sag stain discoloration on freshly cut wood of various kinds; controlling bacterial and fungal lgrowth in clay and pigment slurries of various types which are manufactured for later use in paper coating and paint 3p ' manufacturing for example, and which &re susceptible to degradation by microorganisms during storage and transport; as a hard surface disinfectant to prevent growth of bactexia and fungi on walls, floors, etc.;
and in swimming pools to prevent algae growth.
The control of bacteria and fungi in pulp and paper mill water systems which contain aqueous dispersions of gapermaking fibers is especially important. The uncontrolled buildup of slime produced by the accumulation of bacteria and fungi causes offgrade production, decreased production due to breaks and greater cleanup frequency, increased raw material usage, and increased maintenance costs.
The problem of slime deposits has been aggravated by 1o the widespread use of closed white water systems in the paper industry.
Another important area where control of bacterial and fungal growth is vital is an clay and pigment.
slurries. These slurries are of various clays, e.g.
15 kaolin, and pigments, e.g. calcium carbonate and ' titanium dioxide, and are manufactured usually at a location separate from the end use application, in for example, paper coating and paint manufacturing, and aye then stored and held for later transport to 20 the end use location. Because of the high quality standards foi the paper and paint final products in which the slurry is used, it is essential that the clay or pigment slurry have a very low microorganism count or content so that it is usable in the paper a5 coating or paint manufacturing.
Yet another important area for cantrolling microbial growth is cooling systems such as those .
using cycled up recirculating.cooling towers. Such systems maintain a large body of water for a 30 considerable length of time exposed to the atmosphere under canditions which do not include sufficient aeration and exposure to sunlight to provide contxol of microbial, especially bacterial and fungal, 3776H -5- G-1.578 growth. In particular, many cooling towers use fill composed of beads of synthetic polymer or other materials, in order to extend the amount of heat exchange surface area, and this type of construction ~ greatly aggravates the problem of microbiological growth, since it provides an ideal physical environment for the propagation of. troublesome microbes. Unchecked, such microorganisms flourish and produce colonies extensive enough to give rise to to problems of 'biofilm blockage of heat exchange surfaces, as well as clogging of the components of the water transporting apparatus used in operating the cooling system. The synergistic combinations of the present invention providelnot only excellent control of microbial growth in such systems, but also .inhibit the deposition of calcium carbonate scale as well.
The synergistic combination of the present invention has been found especially useful in controlling t',he harmful effects of microorganisms in water or aqueous media. Systems which utilize circulating water or aqueous media become infected with microorganisms and experience substantial impairment of their efficiency when deposits of the microorganisms build up in the system. The deposits, called slimes, coat the walls of tanks arid other vessels, and any machinery or processing equipment which is employed,, and create blockages in pipes and valves. The slime formation promotes corrosion of metal surfaces and facilitates the deterioration of wooden towers.' The slimes also create.discolorations and other imperfections in any products being produced, forcing costly shutdowns. Control of microorganisms in aqueous media is paxticulary 3776H -s- C-1578 important where there are dispersed particles or fines in the aqueous media, e.g.., dispersed cellulosic fibers and dispersed fillers and pigments in papermaking, and dispersed pigments in paint manufacture.
The synergistic antimicrobial combination of the present invention may also be utilized for agricultural and animal health applications, for example in preventing or minimizing the growth of harmful bacteria, yeast, and/or molds on plants, trees, fruit, seeds or soil. The synergistic .
combination may be useful in treating seed to prevent microorganism, particularly fungal attack. The synergistic combination may also be useful in protecting animal dip compositions against the buildup of microorganisms, and for this purpose may be combined with a veterinary animal dip parasiticide and an acceptable carrier.
2. Prief Description of the Prior Art Crier, et a1., U.S. Pat. Nos. 3,833,731 and 3,877,922; and Harmetz et al., U.S. Pat. Nos.
3,873,597 describe 2-bromo-2-bromomethyl-glutaronitrile and related compounds and their use~as antibacterial, antifungal and algicidal ag~nts.
8inton et a1. U.S. Pat. No. 3,065,123 describes a process for controlling microorganisms in water and aqueous media by the addition of certain 1:2-benzisothiazolones.
British Pat. No. 1,531,431 describes treatment with N-alkyl 1,2-benzisothiazolin-3-tines for cori~trolling microorganisms in watex-based paints and adhesives, water-oil emulsions, and metalworking fluids.
Gazzard et al. U.S. Pat.. No. 3,970,755 describes biocidal compositions comprising certain quaternary ammonium compounds and 1,2-benzisothiazolin-3-ones.
U.K. Pat. No. 1,458,041 describes a synergistic biocidal composition, especially for aqueous systems, containing isothiazolin-3-ones and 2-thiono-tetrahydro-1,3,5-thiadiazines.
U.S. Pat. No. 4,604,405 discloses synergistic antimicrobial admixtures of 2-bromo-2-bromomethyl-glutaronitrile and 2,2-dibromo-3-nitrilopropionamide.
U.S. Pat. No. 4,612,328 discloses synergistic antimicrobial admixtures of 2-bromo-2-bromomethyl-glutaronitrile and methylene bis(thiocyanate).
U.S. Pat. No. 4,655,815 discloses synergistic antimicrobial admixtures of 2-bromo-2-bromomethyl-glutaronitrile and a formaldehyde donor.
U.S. Pat. No. 4,830,657 discloses synergistic antimicrobial admixtures of 2-bromo-2-bromomethyl-glutaronitrile and 1,2-benzisothiazolin-3-ones.
However, there is no suggestion in any of the above references of the synergistic antimicrobial combination of the present invention.
The present invention. relates to a synergistic antimicro'bial admixture comprising an antimicrobially effective amount of ~776H -8- C-1578 (A) a polyether polyamii~o ethylene phosphonate of the following formula:
M203p - H2C R R CH2POgM2 ~ , N - CH - CH2 -(- OCH2 - CH -)n - N
and. optionally the N-oxides thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable cation; and each R may be the same or. different and is independently selected from hydrogen and methyl; AND
(H) one ox. more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
2o methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole.
glutaraldehyde;
potassium dimethyldithiocarbamate;
29 . 5-chloro-2-methyl-4-isothiazolin-3-one;
2-methyl-4-isothiazolin-3-one;
tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane;
30 A preferred subclass of compositions is that wherein for component (A.), in the above formula, M is hydrogen, R is methyl, and n is from about 2 to about 3, moat preferably an average of about 2.6.
U) ~ U c~
The present invention also 'relates to a method of inhibiting microbial growth,, comprising contacting the microbial growth with an antimicrobially effective amount of an admixture comprising:
(A) a polyether polyamino methylene phosphonate of the following formula:
M20gP - H2C R R CH2POgM2 N - CH - CH2 -(- OCH2 - CH -)n - N
M2o3p - $2~ . ~ CH2P03M2 and optionally the N-oxides thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable cation; and each R may be the same or different and is independently selected from hydrogen and methyl; AND
(B) one ar more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole.
glutaraldehyde;
potassium dimethyldithiocarbamate; , ' S-chloro-2-methyl-4-ieothiazolin-3-one;
2-methyl-4-isot~hiazolin-3-one;
'tetrahydro-3,5-dimethyl-2,H-1,3, .
5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane;
.~ <> ~~
J v e) The present invention stilh further relates to a method of inhibiting the formation, deposition and adherence of scale-forming salts in an aqueous system, while at the same time inhibiting microbial growth in said system, comprising the step of adding to said system an amount sufficient to establish a concentration of from 1 to I00 mgjL of an admixture of a polyether polyamino methylenephosphonate of the formula above and~a non-oxidizing biocide~which is to one or more members selected from the group consisting essentially of those recited above.
pFTpTLED DESCRIP'~'Tn't~ Off' THH INVErTTTnN
The first component of the synergistic antimicrobial admixture of the present invention comprises a polyether polyamino methylene phosphonate of the formula:
N - CH - CH2 -(- OCH2 - CH -)n - N
M203P - $2C CH2POgMx.
and optionally the N-axides thereof; where n is an integer or fractional integer which is, or on average is,, from about 2 to about 12,~inclusive; M is hydrogen or a suitable cation; and each R may be the 3o same or different and is independently selected fiom hydrogen and methyl.
3776H -11- c-1578 A preferred subclass of compositions of the abbve formula is that wherein M is hydrogen, R is methyl, and n is from about 2 to about 3, mos~ preferably an average of about 2.6.
In Order to obtain good synergistic antimicrobial results, and also particularly to obtain as well high levels of control of scale deposits, especially under severe conditions of high pH and high calcite concentrations, it has been found that there are 1o certain essential components of the structure of the polyether polyamino methylene phosphonates which are necessary to provide that performance. Thus, e.g., the tetra(aminophosphonate) portion of the structure is essential. Whether these. groups are present 15 initially in the phosphoric acid form or as an alkali .metal or other salt of the acid, has no real bearing on the performance of the overall molecule. At the pH°s under whack the compositions of the present invention function, they are, and must be, in their 20 ionized form. Thus, it is not critical Whether °°M~°
is hydrogen or a suitable nation, and the selection of an appropriate salt form is well within the skill of the art. xn addition to alkali metal salts, ammonium salts: NH4, or ammonium derivative 25 salts: NR~ (R = alkyl, etc.), or mixtures thereof, may be used. Alkali metal salts are the most simple, and are preferred for that reason.
The polyether,polyamino methylene phosphonate may be in the N-oxide form: N ~ 0. This group confers 30, significant resistance to degradation.
Another desirable feature of the .polyether phosphonates and N-oxides thereof useful in the synergistic antimicrobial admixtures and methods of 3776H .-12- C-1578 the present invention is the isopropyl group which bridges the diphosphonomethylamino group and the polyether group.
The next structural element of the polyether phosphonates and N-oxides to be considered is the polyether moiety:
R
-~-OCH2 - CH -)n_ 1p R may be hydrogen or methyl, and thus the polyether moiety is either polyoxyethylene or polyoxypropylene, with the polyoxypropylene being preferred. Since~the polyether polyamino methylene phosphonates are prepared by phosphonomethylation of the appropriate diamine, the character of the polyether moiety will depend upon the way in which the amine starting material is made. Processes for making such polyether diamines are known in the art; and 'attention is directed particularly to US 3,236,895, which describes preparation of a variety of po:Lyether diamines especially useful in preparing the ~~
phosphonate Final products used in the present invention.
In accordance with, the processes set out in US
a~236,895 and related processes described in the prior a,rt, it is possible to prepare any one o~ a number of desired polyether diamines within the scope of the present invention. In the general formula for the polyether polyamino methylene phosphonates used herein,.the polyether moiety is simply represented by the formula above.' Since R may be hydrogen or methyl, both ethyleneoxy and propyleneoxy units are possible, as already mentioned. Moreover, R is to. be independently chosen,.i.e., ethyleneoxy and ~~~u~~~
3776x -13- C-x.578 propyleneoxy units may alternate in various patterns, including blocks of each, or they may be all one or the other. For example, the. following are just some of the polyether segments which might be prepared to form the basis for the corresponding diamines, which would then be used to make phosphonates within the scope of the present invention (where EO =
ethyleneoxy, and PO = propyleneoxy):
E0; P0; EO-E0; PO-P0; EO-P0; EO-EO-E0;
PO-PO-P0; EO-EO-P0; EO-PO-P0; EO-PO-E0;
PO-EO-P0; E0-EO-.EO-E0; PO-PO-PO-P0; EO-PO-PO-P0;
EO-EO-PO-P0; EO-EO-EO-P0; EO-PO-EO-P0;
E0-PO-PO-EO; PO-EO-EO-PO
15 ~ In the above examples, "n" in the main formula would be an integer of from 1 to 4. Since °'n" is defined as being from 1 to 1z, an even larger number of possible polyether moieties is included. However, it has been found that generally the polyether 2o phosphonates of lower molecular weight, i.e., where "n" is a smaller integer, are those which are preferred. E;Kamples of some of these preferred phosphonates are shown in the table below, where Z =
methylenephosphonate:
~.~~~.~.~~~a Rz Ra Rb Z2-N-CHCH2-(OCHzCH)a -(OCH2CH)b -NZZ
1~ d . No . ~ ~ ~Z_ ~a_ -$b_ 2.6" 0 CHg CHg ___ C 2 0 CH3 CHg "' H 8. 5'~' 1 CHI ~ . H CHI
5.6* o eH3 cH3 __ F ~ 2 0 H H ___ C 3 0 H H ___ H . ~ .0 CH3 ~. CHg ___ J ~E 0 H CHg ___ * ~ the value of "n" on average.
It will be; noted from the table above that in several .cases, "n" has an average value, i.e., the number of repeating ethyleneoxy or propyleneoxy units may vary. Thus, it 'is possible to have a mixture of varying chain lengths of pol o .
y xyethylene or polyoxypropylene in the final product. This is also contemplated to be within the scope of the present invention, so long as the requirements with respect to the limit o~ "n" are observed. Consequently, while "n" is merely defined as an integer or fractional integer which~is, or on average is, from about 2 to about 12, it has two aspects. It defines the total of the number of repeating ethyleneoxy ~:~.~~~8~
and/or propyleneoxy units considered separately, and thus if "n" is, e.g., 4, it.includes G. propyleneoxy units, 3 propyleneoxy units and 1 ethyleneoxy unit, 2 propyleneoxy units and 2 ethyleneoxy units, and so forth. The value of ~'n" may also represent an average number, and this is always the case, of course, when it is a fractional integer. In this case, for each of the ethyleneoxy and/or propyleneoxy units considered separately, mixtures of these units may be present so as to give an average value for ~'n'~. For example, in the table above, for Td. No. D, the total of ~'a°' and "b°' is 9.5, which is the value of '~n'~. What is described is a mixture of polyether phosphonates in which all of them have an isopropyl bridging group and an ethyleneoxy moiety, but the repeating propyleneoxy units are such that on average their value is about 8.5.
The numbex of repeating ethyleneoxy or oxypropylene units, designated by the subscript ''n", 2o determines the total molecular weight of the overall polyether phosphonate. It has been found .that in order to achieve optimum synergistic antimicrobial results, as well as, particularly, provide adequate scale control under the severe conditions of use defined herein, it is necessary that '~n" be an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive.' As discussed above, the reason for "n~' being potentially a fractional integer arises from the fact , that the primary diamine from which the polyether polyamino methylene phosphonates are prepared by.
phosphonomethylation may be a mixture of polyethers 3776~i -16- c-157$
in which '°n°' is two or more of '2, 3, 4, 5 and so forth, in varying proportions. for example, a preferred polyether polyamino methylene phosphonate for use in the compositions and methods of the present invention has a molecular weight of approximately 632 and the value of °'n" on average is about 2.6. Thus, this type of polyether phosphonate has a molecular weight distribution, i.e., of the various polyoxypropylenes which make it up., and this to distribution is represented by a fractional integer average value for "n". But, it is also within the scope of the present invention for "n" to be a whole integer, e.g., "3", which usually designates a single molecular weight and not a molecular weight 15 distribution.
The polyether phosphonates and corresponding N-oxides of the synergistic antimicrobial admixtures and methods of the preeent invention are prepared first by phosphonomethylation of the appropriate 20 primary diamine which already contains the polyoxyethylene and polyoxypropylene moieties, followed by an oxidation step which provides the N-oxide moieties..
Such primary amine starting materials and their 2~ method of preparation are, well known. The phosphonomethylation of the primary diamiz~e is then carried out by a Mannish reaction such as that described in K. Moedritzer and R. Irani, J. Org n~t~
Chem. 31(x) 1603-7, "The Direct Synthesis of 3o alpha-Aminomethyl phosphonic Acids; Mannish-Type Reactions with Orthophoaphoroue Acid", May 1966. In a typical. reaction, the primary diamine is added to a mixture,of phosphorous acid and water, and ~$_~~~%~
3776Ii ~17- c-1578 concentrated hydrochloric acid ~is then added slowly, after which the reaction mixture is heated to reflux with addition of aqueous formaldehyde.
Although the general structural formula employed ' herein indicates that the nitrogen atom is completely phosphonomethylated, as a practical matter, preparation of the polyether polyamino methylene phosphonates of the present invention, as described in detail further below, usually results in only to about 80 to 90% phosphonomethylation. Other side products give N-substitution with H, CH3, CH24H, etc. It is not practical, as a matter of simple production economics, however, to isolate and purify the completely phosphonomethylated compounds, since the side products just described do not interfere ,With scale deposit inhibition. Such side products, are consequently, usually allowed to remain, and the test data set out further below is based on test samples containing such side products. Consequently, the activity '.evels obtained would be even higher were 100% active compound teeing tested.
Once the desired phosphonomethylated polyoxypropylene diamine has been prepared as described above, the N-oxide final product of the present invention is then prepared by a otep of oxidation, which may be accomplished, e.g., simply by adding hydrogen peroxide to a basic solution of the phosphonomethylated diamine and heating the reaction mixture, which gives high yield's of the N-oxide final o product. Of course, it is also possible to use other well known techniques for~carrying o~t~such a step of oxidation, and any number of these may be successfully employed.
t~ s~
3776I3 -18- c-1578 When, any of the polyether polyamino methylene phosphonate components of the synergistic antimicrobial admixtures of the present invention are used to inhibit microbial growth, especially in an aqueous system, they can be effectively employed for that purpose when added in amounts sufficient to establish a concentration in said aqueous~system of from 1 to 100 mg/L. Preferably, the amount added will be sufficient to establish a concentration of ZO from 5 to 75 mg/L, and most preferably, the amount added will be sufficient to establish a concentration of from 10 to 50 mg/L of the composition. For example, a typical dosage amount would be 25 mg/L.
Tt is understood, however, that many f actors, of the 15 type which have been explained in detail with regard ' to the background to the present invention, will determine the actual amount of the polyether phosphonate components of the present invention which will be added in order to achieve the maximum amount 20 of inhibition of microbial growth in that system.
The ,calculation of those amounts is well within the skill of the artisan in this field.
COMPONENT (B) The second component of the synergistic ar~timicrobia~. admixtures of the pxesent inve;~tian is one or more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole.
glutaraldehyde;
potassium dimethyldithiocarbamate; .
5-chloro-2-methyl-4-isothiazolin-3-one;
2-methyl-4-isothiazolin-3-one;
1o tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane;
All of these non-oxidizing biocides are commercially available and used extensively in various industrial 15 applications. xhey are. diverse in chemical structure and only have in common the fact that they act synergistically with the polyether phosphonate components (A) when used in admixture to inhibit microbial growth.
20 When any of the non-oxidizing biocides components of the synergistic antimicrobial admixtures of the present invention are used to inhibit microbial growth, especially in an aqueous system, they can be effectively employed fox that purpose when added in 25 amounts sufficient to establish a concentration in said aqueous system of from 0.5 to 50 mg/L.
Preferably, the amount added will be sufficient to establish.a concentration of from 1.0 to 25 mg/L, and most preferably, the amount added will be sufficient 3o to establish a concentration of from 3.0 to 20 mg/L
of the composition. However, it will be appreciated that the.dosage of the individual non-oxidizing biocide will vary from biocide to biocide because of . their diversity, and the most accurate guide to the correct dosage is the dosage at which each, individual non-oxidizing biocide is conventionally applied to achieve inhibition of microbial growth 'in various applications areas. It will be understood, then, that many factors, of the type which have been explained in detail with regard to the background to the present invention, will determine the actual amount of the non-oxidizing biocides components of the present invention which will be added in order to achieve the maximum amount of inhibition of microbial growth in that system. The calculation of those amounts is well within the skill of the artisan in this field.
The proportions~of the two components of the synergistic.combination are dictated by the dosage ' levels of each component, based~on 100% active ingredient,.which will be employed in each end use . application. The recommended dosage levels are described in detail below.
The synergistic antimicrobial admixture active ingredient components of the antimicrobial compositions of the present invention may be used in diverse 'formulations: solid, including finely divided powders and,granular materials; as well as 2S liquid, such as solutions, emulsions, suspensions, concentrates, emulsifiable concentrates, slurries and the like, depending upon the application intended, and the formulation media desired. Further, when the ' synergistic an~imicrobial combination ie liquid, it may be employed neat or may be incorporated into various formulations, both solid and liquid, as an adsorbate on suitable inert carriers such as talc, clays, diatomaceous earth and the like.
~.~ J1 ~ t~ t~
°-21- C-1578 Thus, it will be appreciated that the synergistic antimicrobial admixtures may be employed to form antimicrobial formulations containing the combination as the essential active ingredient, which formulations may also contain a variety of carrier materials adaptable to industrial and agricultural applications including finely divided dry or liquid diluents, extenders, clays, diatomaceous earth, talc and the like, or water and various organic liquids such as lower alkanols, kerosene, benzene, toluene and other petr.oleum'distillate fractions or mixtures thereof .
It will be understood also that the synergistic antimicrobial admixture active ingredients may be used in combination with other antimicrobial materials. For example, the combination can be further combined with other fungicides and bactericides ~>uch as 2-(4~-thiazolyl)benzimidazole, sorbic acid, propionic acid, mycostatin, sodium diacetate, trichomycin amphotericin, griseofulvin, undecylenic acid, esters of parahydroxybe~zoic acid, chlorguinaldol, 5,7-dichloro-8-hydroxyquinoline, sodium-o-phenylphenate, o-phenylphenol, biphenyl chlorinated phenols, sodium benzoate in appropriate concentrations and in appropriate instances so as to combine the action of each to obtain particularly useful results. Such combinations might' find particular application in the preparation of germicidal soaps, in the production of cosmetics and 0 , aqueous coatings and in combatting paper mill slime accumulations. It is quite clear also that the synergistic antimicrobial admixtures can be combined with other algicidal agents such as benzalkonium chlorides and other quaternary ammonium compounds to ~~.~~J.~.u~
3z7b~z -a2- c-15~$
obtain formulations particularhy suitable to special problems of algae control.
Thus, in accordance with the present invention there is provided a method of killing or inhibiting the growth or propagation of at least one of:
bacteria, yeast, mold, and algae, in dormant, immature, developing and/or mature stages, comprising contacting said bacteria, yeast, mold, or algae, with a bactericidally,~fungicidally, or algicid~ally effective amount of the synergistic antimicrobial admixtures comprising a polyether phosphonate and one or more specifically recited non-oxidizing biocides.
As noted above, the instant invention is based upom the discovery that the synergistic antimicrobial admixtures described above are effective in controlling the growth of bacteria, yeast, fungi and algae in industrial and possibly agricultural applications. It is likely, for example, that the combination is an effective antimicrobial for the 2o destruction or control of soil fungi and bacteria and for the protection of seeds, bulbs, and plants, Also, it may be useful as an effective algicide in the treatment of pools and ponds, cooling water systems and the like. The synergistic antimicrobial ~5 combination of this invention may be useful not only against bacteria and fungi responsible for stunting growth, and even destruction of many types of crop-producing plants, but also against those causing degradation and deterioration of many types of industrial products including, fox example, paper, leather, wood preservation, te~ttiles, aqueous systems such as adhesives, resins, drilling fluids,~pigment dispersions and latex paints and oleoresinous coatings whose films are particularly vulnerable to 2~~~~~
3776H -23-- ' C-1578 the destructive action of fungi. The formation of.
slime by microorganisms in the water from cooling towers can be minimized with the present invention, thus avoiding the deterioration, corrosion, fouling and decreased efficiency of the cooling system which would otherwise result. The large economic losses encountered in pulping and papermaking operations caused by the accumulation of bacterial and fungal slimes in various parts of the system can be eliminated to a significant extent by use of the synergistic admixtures described herein.
The antimicrobial methods of treatment of the present invention involve contacting the microorganisms involved with the synergistic antimicrobial admixtures. This can be accomplished .either by simple addition of the two or more components of the combination together as a single composition, or by addition of the two or moss components separately. Such separate co-administration can either be at the same time or at different times. The net effect will be the same: the article or system being treated will ultimately have incorporated therein or have applied thereto the desired dosage concentration of each component.
In the treatment of aqueous systems, such as cooling water systems, paper and pulp mi~.l~syetems, pools, ponds, lagoons, lakes, etc., to control the growth and/or propagation formation of microorganisms the two components of the combination may be added together as a single compbsition~at orie or at multiple points in the system, or may be added separately, at the same or at different points and/or times of, introduction, thus resulting in the desired antimicrobial effect.
The antimicrobial activity of the synergistic antimicrobial admixtures and individual components thereof described above has been confirmed using standard laboratory techniques. They have been found to be effective, for example, in inhibiting bacteria including ~lebsiella uneumon~ae pneumoniae, Pseudomonas aeruginosa, and I~icrococcus sp. They 1o should also be effective against other bacteria and fungi including Penicilli~m species, ~accharomtCes species, including ~. cerevisiae, Candida species;
Fusarium species, Asnergillus species, and Cenhalospo~y'm species. Such bacteria and/or fungi 15 commonly axe found on cereal and grain products, in ' clay and pigment slurries, in oils, on fruits and vegetables and on cosmetics, leather, electrical insulation, textiles and numerous other materials capable of supporting their growth. Also, such 20 bacteria and/or fungi may be found on plants, seeds, fur and wood and in soils. Further, they may be used to control overgrowth of algae such as rhlor ~~a sp.
including ~. ,pyrenoidosa.
As noted above, it is expected that growth of 25 various harmful fungi and bacteria existing in soil can be eliminated or limited by use of formulations containing the synergistic antimicrobial admixtures described herein. The term ~~sai~.~~ as used here is intended to include all media capable of supporting 3o growth of plants and may include humus, sand, manure, compost, artificially created plant growth solutions and the like.
., The synergistic antimicrobial admixtures described above~have activity against bacteria, yeast, mold, and/or algae when employed at appropriate levels of concentration and may be used to inhibit growth of these organisms. It will be obvious to those skilled in the art that the reguired effective concentration'will var with y particular organisms and in particular applications. In general, however, effective fungicidal, bactericidal and algicidal response is obtained then when the synergistic antimicrobial admixture is employed in 1o concentrations ranging between 1 and 200 ppm (parts per million), preferably 1 and 50 ppm, of polyether phosphonate; and between 1 and 1000 ppm, preferably 1 to 880 ppm, of non-oxidizing biocide, and in a weight ratio of polyether phosphonate/non-oxidizing biocide 15 (on an active basis) of.10:1 to 1:5, preferably 5:1 to 1:3, and even more preferably 3:1 to 1:2. Such levels may be achieved by the administration of the two components of the admixture together as a single composition (optionally comprising other 2o antimicrobial materials and/or inert carriers and excipients), or separately at the same or different points and/or times of introduction.
For other applications of the type described above, amounts of from 0.005 to 1.0% by weight, based 25 on weight of the substrate being treated, of the synergistic antimicrabial combination of the present invention is incorporated into, spxayed onto, used to dip, or otherwise applied to the substrate to be treated in order to prevent growth of bacteria, fungi 30 (including yeasts and molds) and algae.
l ~~~ n Of course, the precise dosages of the components which will be employed depends upon a number of factors. First, the dosage is indicated in parts per million (ppm), which refers to the concentration of the active ingredient in the environment being treated, for example, the concentration of DGH in a cooling water system. This concentration is based on 1~0% active ingredient for convenience in evaluating and comparing test data. In actual practice, ZO however, various percentages of active ingredient may actually be used, with the balanc.e~of the composition being added comprising conventional excipients such as dispersants, stabilizers, preservatives, co-solvents, diluents, and the like.
The components of the synergistic antimicrobial admixtures of the present invention may be added to an article or system to be treated as separate entities, or as combination. The two components may be combined simply as active ingredients, or may 20 additionally be combined with commonly employed carriers and excipients, as described above.
Altk~ough it is believed that the synergistic activity exhibited by the two components is due to their presence as discrete chemical entities, 25 chemical reaction between the two and the formation of adducts or cross-reaction products ie possible.
Such additional active species are also encompassed within the scope of the instant invention.
The following examples will serve to further 30 illustrate the present invention but should not be construed in any Way as being a limitation on the scope thereof .
3776iI -27- C-1578 EXAMPLES OF P FFFRRF J~j~$OpIpj~jvjT, Two series of experiments were set up which consisted of 50 ml solutions of deionized water adjusted to pH 9 with sodium hydroxide. A~.1 the experimental solutions were inoculated witkt a mixed environmental bacteria, cagped and held at ambient room temperature. The first series consisted of a control, containing no biocide, and other solutions each containing a non-oxidizing registered biocide at a typical uee 'concentration. The second series consisted of a second control containing only the tetra methylene phosphonate of Jeffamine*D-230 (JMP), and other solutions each containing a non-oxidizing registered biocide at a typical uee concentration plus 25 mg/L active JMP. At three hours of contaet tame, a one milliliter aliquot was removed from each solution and bacteria bevels Were measured using the standard plate count procedure.
2o This bacterial. measurement was repeated again at 24 hours of contact time. .
percent Bactar~a'~ Kay, 2Q mg/L Didecyl 20 mg/1. Didecyl Dimethyl Ammonium Dimethyl Ammonium Chloride and Chlor d~ 25 ma/~",JMP
3 Houre Kill ~ 90% 99%
24 Hours Kill 83% . 89%
377s~z -28- ~-1578 Example 2:
12.8 mg/L
12.8 mg/L Dodecylguanidine Dodecylguanidine hydrochloride and Hy,~rochloride 25 mall ~P
3 Hours Kill g0% 9g%
24 Hours Kill 67% 89%
dam 1~ a 3:
7.5 mg/L Methylene 7.5 mg/Z Methylene Bisthiocyanate Bisthioc;,canate and 25 mg./L JMP
3 Hours Kill 70% 93%
24 Hours Kill 17% 8g%
gprcent Bacterial Kill 3.75 mg/L
3.75 mg/L 2,2-Dibromo-3-N~r~lo-Prop;ona<m~de and 25 ma/L SIP
3 Hours Kill 90% 99%
24 Hours Kill 0% 89%
Percent Bact ia1 xill 15 mg/I. 15 mg/Ir 2-2-(Thiocyano . (Thiocyano Methylthio) Methylthio) Benzothiazole/ Benzothiazole/
Methylene Bisthiocyanate Bisthiocvanate and 25 me/L 3MP
3 Hours Kill 6s% 99%
24 Hours Kill 0% 83,°g Gontro~ Ba t r;p~'jLevel_s Control ~~l Control #2 ~Io Additives 25 mg_/L ,'(~P
3 Hours Count 250,000 3,500,000 24 Hours Couaat 30,000 175,000 Following the procedures described above, but at pH 7.0, the results set out below were obtained.
~c~iij~i a 7 Percent 3acterial Kill 27 mglT. 25 mg/L 35 mgll.
glutara~dehyd~ Potassium 5-chloro-2-methyl-Dimethyl- 4-isothiazolin-3-d;thioca b mate one and 2-methyl-4-isoth~aio~~.n-3-one 3 Hours Kill 64% 37% 39~
40 mg/L 59 mg/I.
tetrahydro-3- 1,2-dibramo-2,4-5-dimethyl-2-,H-1, r~~.~a~obutane 3, 5-thiadiazin-2~
1 S Glaione 3 Hours Kill 53Z 39%
a
3,873,597 describe 2-bromo-2-bromomethyl-glutaronitrile and related compounds and their use~as antibacterial, antifungal and algicidal ag~nts.
8inton et a1. U.S. Pat. No. 3,065,123 describes a process for controlling microorganisms in water and aqueous media by the addition of certain 1:2-benzisothiazolones.
British Pat. No. 1,531,431 describes treatment with N-alkyl 1,2-benzisothiazolin-3-tines for cori~trolling microorganisms in watex-based paints and adhesives, water-oil emulsions, and metalworking fluids.
Gazzard et al. U.S. Pat.. No. 3,970,755 describes biocidal compositions comprising certain quaternary ammonium compounds and 1,2-benzisothiazolin-3-ones.
U.K. Pat. No. 1,458,041 describes a synergistic biocidal composition, especially for aqueous systems, containing isothiazolin-3-ones and 2-thiono-tetrahydro-1,3,5-thiadiazines.
U.S. Pat. No. 4,604,405 discloses synergistic antimicrobial admixtures of 2-bromo-2-bromomethyl-glutaronitrile and 2,2-dibromo-3-nitrilopropionamide.
U.S. Pat. No. 4,612,328 discloses synergistic antimicrobial admixtures of 2-bromo-2-bromomethyl-glutaronitrile and methylene bis(thiocyanate).
U.S. Pat. No. 4,655,815 discloses synergistic antimicrobial admixtures of 2-bromo-2-bromomethyl-glutaronitrile and a formaldehyde donor.
U.S. Pat. No. 4,830,657 discloses synergistic antimicrobial admixtures of 2-bromo-2-bromomethyl-glutaronitrile and 1,2-benzisothiazolin-3-ones.
However, there is no suggestion in any of the above references of the synergistic antimicrobial combination of the present invention.
The present invention. relates to a synergistic antimicro'bial admixture comprising an antimicrobially effective amount of ~776H -8- C-1578 (A) a polyether polyamii~o ethylene phosphonate of the following formula:
M203p - H2C R R CH2POgM2 ~ , N - CH - CH2 -(- OCH2 - CH -)n - N
and. optionally the N-oxides thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable cation; and each R may be the same or. different and is independently selected from hydrogen and methyl; AND
(H) one ox. more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
2o methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole.
glutaraldehyde;
potassium dimethyldithiocarbamate;
29 . 5-chloro-2-methyl-4-isothiazolin-3-one;
2-methyl-4-isothiazolin-3-one;
tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane;
30 A preferred subclass of compositions is that wherein for component (A.), in the above formula, M is hydrogen, R is methyl, and n is from about 2 to about 3, moat preferably an average of about 2.6.
U) ~ U c~
The present invention also 'relates to a method of inhibiting microbial growth,, comprising contacting the microbial growth with an antimicrobially effective amount of an admixture comprising:
(A) a polyether polyamino methylene phosphonate of the following formula:
M20gP - H2C R R CH2POgM2 N - CH - CH2 -(- OCH2 - CH -)n - N
M2o3p - $2~ . ~ CH2P03M2 and optionally the N-oxides thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable cation; and each R may be the same or different and is independently selected from hydrogen and methyl; AND
(B) one ar more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole.
glutaraldehyde;
potassium dimethyldithiocarbamate; , ' S-chloro-2-methyl-4-ieothiazolin-3-one;
2-methyl-4-isot~hiazolin-3-one;
'tetrahydro-3,5-dimethyl-2,H-1,3, .
5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane;
.~ <> ~~
J v e) The present invention stilh further relates to a method of inhibiting the formation, deposition and adherence of scale-forming salts in an aqueous system, while at the same time inhibiting microbial growth in said system, comprising the step of adding to said system an amount sufficient to establish a concentration of from 1 to I00 mgjL of an admixture of a polyether polyamino methylenephosphonate of the formula above and~a non-oxidizing biocide~which is to one or more members selected from the group consisting essentially of those recited above.
pFTpTLED DESCRIP'~'Tn't~ Off' THH INVErTTTnN
The first component of the synergistic antimicrobial admixture of the present invention comprises a polyether polyamino methylene phosphonate of the formula:
N - CH - CH2 -(- OCH2 - CH -)n - N
M203P - $2C CH2POgMx.
and optionally the N-axides thereof; where n is an integer or fractional integer which is, or on average is,, from about 2 to about 12,~inclusive; M is hydrogen or a suitable cation; and each R may be the 3o same or different and is independently selected fiom hydrogen and methyl.
3776H -11- c-1578 A preferred subclass of compositions of the abbve formula is that wherein M is hydrogen, R is methyl, and n is from about 2 to about 3, mos~ preferably an average of about 2.6.
In Order to obtain good synergistic antimicrobial results, and also particularly to obtain as well high levels of control of scale deposits, especially under severe conditions of high pH and high calcite concentrations, it has been found that there are 1o certain essential components of the structure of the polyether polyamino methylene phosphonates which are necessary to provide that performance. Thus, e.g., the tetra(aminophosphonate) portion of the structure is essential. Whether these. groups are present 15 initially in the phosphoric acid form or as an alkali .metal or other salt of the acid, has no real bearing on the performance of the overall molecule. At the pH°s under whack the compositions of the present invention function, they are, and must be, in their 20 ionized form. Thus, it is not critical Whether °°M~°
is hydrogen or a suitable nation, and the selection of an appropriate salt form is well within the skill of the art. xn addition to alkali metal salts, ammonium salts: NH4, or ammonium derivative 25 salts: NR~ (R = alkyl, etc.), or mixtures thereof, may be used. Alkali metal salts are the most simple, and are preferred for that reason.
The polyether,polyamino methylene phosphonate may be in the N-oxide form: N ~ 0. This group confers 30, significant resistance to degradation.
Another desirable feature of the .polyether phosphonates and N-oxides thereof useful in the synergistic antimicrobial admixtures and methods of 3776H .-12- C-1578 the present invention is the isopropyl group which bridges the diphosphonomethylamino group and the polyether group.
The next structural element of the polyether phosphonates and N-oxides to be considered is the polyether moiety:
R
-~-OCH2 - CH -)n_ 1p R may be hydrogen or methyl, and thus the polyether moiety is either polyoxyethylene or polyoxypropylene, with the polyoxypropylene being preferred. Since~the polyether polyamino methylene phosphonates are prepared by phosphonomethylation of the appropriate diamine, the character of the polyether moiety will depend upon the way in which the amine starting material is made. Processes for making such polyether diamines are known in the art; and 'attention is directed particularly to US 3,236,895, which describes preparation of a variety of po:Lyether diamines especially useful in preparing the ~~
phosphonate Final products used in the present invention.
In accordance with, the processes set out in US
a~236,895 and related processes described in the prior a,rt, it is possible to prepare any one o~ a number of desired polyether diamines within the scope of the present invention. In the general formula for the polyether polyamino methylene phosphonates used herein,.the polyether moiety is simply represented by the formula above.' Since R may be hydrogen or methyl, both ethyleneoxy and propyleneoxy units are possible, as already mentioned. Moreover, R is to. be independently chosen,.i.e., ethyleneoxy and ~~~u~~~
3776x -13- C-x.578 propyleneoxy units may alternate in various patterns, including blocks of each, or they may be all one or the other. For example, the. following are just some of the polyether segments which might be prepared to form the basis for the corresponding diamines, which would then be used to make phosphonates within the scope of the present invention (where EO =
ethyleneoxy, and PO = propyleneoxy):
E0; P0; EO-E0; PO-P0; EO-P0; EO-EO-E0;
PO-PO-P0; EO-EO-P0; EO-PO-P0; EO-PO-E0;
PO-EO-P0; E0-EO-.EO-E0; PO-PO-PO-P0; EO-PO-PO-P0;
EO-EO-PO-P0; EO-EO-EO-P0; EO-PO-EO-P0;
E0-PO-PO-EO; PO-EO-EO-PO
15 ~ In the above examples, "n" in the main formula would be an integer of from 1 to 4. Since °'n" is defined as being from 1 to 1z, an even larger number of possible polyether moieties is included. However, it has been found that generally the polyether 2o phosphonates of lower molecular weight, i.e., where "n" is a smaller integer, are those which are preferred. E;Kamples of some of these preferred phosphonates are shown in the table below, where Z =
methylenephosphonate:
~.~~~.~.~~~a Rz Ra Rb Z2-N-CHCH2-(OCHzCH)a -(OCH2CH)b -NZZ
1~ d . No . ~ ~ ~Z_ ~a_ -$b_ 2.6" 0 CHg CHg ___ C 2 0 CH3 CHg "' H 8. 5'~' 1 CHI ~ . H CHI
5.6* o eH3 cH3 __ F ~ 2 0 H H ___ C 3 0 H H ___ H . ~ .0 CH3 ~. CHg ___ J ~E 0 H CHg ___ * ~ the value of "n" on average.
It will be; noted from the table above that in several .cases, "n" has an average value, i.e., the number of repeating ethyleneoxy or propyleneoxy units may vary. Thus, it 'is possible to have a mixture of varying chain lengths of pol o .
y xyethylene or polyoxypropylene in the final product. This is also contemplated to be within the scope of the present invention, so long as the requirements with respect to the limit o~ "n" are observed. Consequently, while "n" is merely defined as an integer or fractional integer which~is, or on average is, from about 2 to about 12, it has two aspects. It defines the total of the number of repeating ethyleneoxy ~:~.~~~8~
and/or propyleneoxy units considered separately, and thus if "n" is, e.g., 4, it.includes G. propyleneoxy units, 3 propyleneoxy units and 1 ethyleneoxy unit, 2 propyleneoxy units and 2 ethyleneoxy units, and so forth. The value of ~'n" may also represent an average number, and this is always the case, of course, when it is a fractional integer. In this case, for each of the ethyleneoxy and/or propyleneoxy units considered separately, mixtures of these units may be present so as to give an average value for ~'n'~. For example, in the table above, for Td. No. D, the total of ~'a°' and "b°' is 9.5, which is the value of '~n'~. What is described is a mixture of polyether phosphonates in which all of them have an isopropyl bridging group and an ethyleneoxy moiety, but the repeating propyleneoxy units are such that on average their value is about 8.5.
The numbex of repeating ethyleneoxy or oxypropylene units, designated by the subscript ''n", 2o determines the total molecular weight of the overall polyether phosphonate. It has been found .that in order to achieve optimum synergistic antimicrobial results, as well as, particularly, provide adequate scale control under the severe conditions of use defined herein, it is necessary that '~n" be an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive.' As discussed above, the reason for "n~' being potentially a fractional integer arises from the fact , that the primary diamine from which the polyether polyamino methylene phosphonates are prepared by.
phosphonomethylation may be a mixture of polyethers 3776~i -16- c-157$
in which '°n°' is two or more of '2, 3, 4, 5 and so forth, in varying proportions. for example, a preferred polyether polyamino methylene phosphonate for use in the compositions and methods of the present invention has a molecular weight of approximately 632 and the value of °'n" on average is about 2.6. Thus, this type of polyether phosphonate has a molecular weight distribution, i.e., of the various polyoxypropylenes which make it up., and this to distribution is represented by a fractional integer average value for "n". But, it is also within the scope of the present invention for "n" to be a whole integer, e.g., "3", which usually designates a single molecular weight and not a molecular weight 15 distribution.
The polyether phosphonates and corresponding N-oxides of the synergistic antimicrobial admixtures and methods of the preeent invention are prepared first by phosphonomethylation of the appropriate 20 primary diamine which already contains the polyoxyethylene and polyoxypropylene moieties, followed by an oxidation step which provides the N-oxide moieties..
Such primary amine starting materials and their 2~ method of preparation are, well known. The phosphonomethylation of the primary diamiz~e is then carried out by a Mannish reaction such as that described in K. Moedritzer and R. Irani, J. Org n~t~
Chem. 31(x) 1603-7, "The Direct Synthesis of 3o alpha-Aminomethyl phosphonic Acids; Mannish-Type Reactions with Orthophoaphoroue Acid", May 1966. In a typical. reaction, the primary diamine is added to a mixture,of phosphorous acid and water, and ~$_~~~%~
3776Ii ~17- c-1578 concentrated hydrochloric acid ~is then added slowly, after which the reaction mixture is heated to reflux with addition of aqueous formaldehyde.
Although the general structural formula employed ' herein indicates that the nitrogen atom is completely phosphonomethylated, as a practical matter, preparation of the polyether polyamino methylene phosphonates of the present invention, as described in detail further below, usually results in only to about 80 to 90% phosphonomethylation. Other side products give N-substitution with H, CH3, CH24H, etc. It is not practical, as a matter of simple production economics, however, to isolate and purify the completely phosphonomethylated compounds, since the side products just described do not interfere ,With scale deposit inhibition. Such side products, are consequently, usually allowed to remain, and the test data set out further below is based on test samples containing such side products. Consequently, the activity '.evels obtained would be even higher were 100% active compound teeing tested.
Once the desired phosphonomethylated polyoxypropylene diamine has been prepared as described above, the N-oxide final product of the present invention is then prepared by a otep of oxidation, which may be accomplished, e.g., simply by adding hydrogen peroxide to a basic solution of the phosphonomethylated diamine and heating the reaction mixture, which gives high yield's of the N-oxide final o product. Of course, it is also possible to use other well known techniques for~carrying o~t~such a step of oxidation, and any number of these may be successfully employed.
t~ s~
3776I3 -18- c-1578 When, any of the polyether polyamino methylene phosphonate components of the synergistic antimicrobial admixtures of the present invention are used to inhibit microbial growth, especially in an aqueous system, they can be effectively employed for that purpose when added in amounts sufficient to establish a concentration in said aqueous~system of from 1 to 100 mg/L. Preferably, the amount added will be sufficient to establish a concentration of ZO from 5 to 75 mg/L, and most preferably, the amount added will be sufficient to establish a concentration of from 10 to 50 mg/L of the composition. For example, a typical dosage amount would be 25 mg/L.
Tt is understood, however, that many f actors, of the 15 type which have been explained in detail with regard ' to the background to the present invention, will determine the actual amount of the polyether phosphonate components of the present invention which will be added in order to achieve the maximum amount 20 of inhibition of microbial growth in that system.
The ,calculation of those amounts is well within the skill of the artisan in this field.
COMPONENT (B) The second component of the synergistic ar~timicrobia~. admixtures of the pxesent inve;~tian is one or more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole.
glutaraldehyde;
potassium dimethyldithiocarbamate; .
5-chloro-2-methyl-4-isothiazolin-3-one;
2-methyl-4-isothiazolin-3-one;
1o tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane;
All of these non-oxidizing biocides are commercially available and used extensively in various industrial 15 applications. xhey are. diverse in chemical structure and only have in common the fact that they act synergistically with the polyether phosphonate components (A) when used in admixture to inhibit microbial growth.
20 When any of the non-oxidizing biocides components of the synergistic antimicrobial admixtures of the present invention are used to inhibit microbial growth, especially in an aqueous system, they can be effectively employed fox that purpose when added in 25 amounts sufficient to establish a concentration in said aqueous system of from 0.5 to 50 mg/L.
Preferably, the amount added will be sufficient to establish.a concentration of from 1.0 to 25 mg/L, and most preferably, the amount added will be sufficient 3o to establish a concentration of from 3.0 to 20 mg/L
of the composition. However, it will be appreciated that the.dosage of the individual non-oxidizing biocide will vary from biocide to biocide because of . their diversity, and the most accurate guide to the correct dosage is the dosage at which each, individual non-oxidizing biocide is conventionally applied to achieve inhibition of microbial growth 'in various applications areas. It will be understood, then, that many factors, of the type which have been explained in detail with regard to the background to the present invention, will determine the actual amount of the non-oxidizing biocides components of the present invention which will be added in order to achieve the maximum amount of inhibition of microbial growth in that system. The calculation of those amounts is well within the skill of the artisan in this field.
The proportions~of the two components of the synergistic.combination are dictated by the dosage ' levels of each component, based~on 100% active ingredient,.which will be employed in each end use . application. The recommended dosage levels are described in detail below.
The synergistic antimicrobial admixture active ingredient components of the antimicrobial compositions of the present invention may be used in diverse 'formulations: solid, including finely divided powders and,granular materials; as well as 2S liquid, such as solutions, emulsions, suspensions, concentrates, emulsifiable concentrates, slurries and the like, depending upon the application intended, and the formulation media desired. Further, when the ' synergistic an~imicrobial combination ie liquid, it may be employed neat or may be incorporated into various formulations, both solid and liquid, as an adsorbate on suitable inert carriers such as talc, clays, diatomaceous earth and the like.
~.~ J1 ~ t~ t~
°-21- C-1578 Thus, it will be appreciated that the synergistic antimicrobial admixtures may be employed to form antimicrobial formulations containing the combination as the essential active ingredient, which formulations may also contain a variety of carrier materials adaptable to industrial and agricultural applications including finely divided dry or liquid diluents, extenders, clays, diatomaceous earth, talc and the like, or water and various organic liquids such as lower alkanols, kerosene, benzene, toluene and other petr.oleum'distillate fractions or mixtures thereof .
It will be understood also that the synergistic antimicrobial admixture active ingredients may be used in combination with other antimicrobial materials. For example, the combination can be further combined with other fungicides and bactericides ~>uch as 2-(4~-thiazolyl)benzimidazole, sorbic acid, propionic acid, mycostatin, sodium diacetate, trichomycin amphotericin, griseofulvin, undecylenic acid, esters of parahydroxybe~zoic acid, chlorguinaldol, 5,7-dichloro-8-hydroxyquinoline, sodium-o-phenylphenate, o-phenylphenol, biphenyl chlorinated phenols, sodium benzoate in appropriate concentrations and in appropriate instances so as to combine the action of each to obtain particularly useful results. Such combinations might' find particular application in the preparation of germicidal soaps, in the production of cosmetics and 0 , aqueous coatings and in combatting paper mill slime accumulations. It is quite clear also that the synergistic antimicrobial admixtures can be combined with other algicidal agents such as benzalkonium chlorides and other quaternary ammonium compounds to ~~.~~J.~.u~
3z7b~z -a2- c-15~$
obtain formulations particularhy suitable to special problems of algae control.
Thus, in accordance with the present invention there is provided a method of killing or inhibiting the growth or propagation of at least one of:
bacteria, yeast, mold, and algae, in dormant, immature, developing and/or mature stages, comprising contacting said bacteria, yeast, mold, or algae, with a bactericidally,~fungicidally, or algicid~ally effective amount of the synergistic antimicrobial admixtures comprising a polyether phosphonate and one or more specifically recited non-oxidizing biocides.
As noted above, the instant invention is based upom the discovery that the synergistic antimicrobial admixtures described above are effective in controlling the growth of bacteria, yeast, fungi and algae in industrial and possibly agricultural applications. It is likely, for example, that the combination is an effective antimicrobial for the 2o destruction or control of soil fungi and bacteria and for the protection of seeds, bulbs, and plants, Also, it may be useful as an effective algicide in the treatment of pools and ponds, cooling water systems and the like. The synergistic antimicrobial ~5 combination of this invention may be useful not only against bacteria and fungi responsible for stunting growth, and even destruction of many types of crop-producing plants, but also against those causing degradation and deterioration of many types of industrial products including, fox example, paper, leather, wood preservation, te~ttiles, aqueous systems such as adhesives, resins, drilling fluids,~pigment dispersions and latex paints and oleoresinous coatings whose films are particularly vulnerable to 2~~~~~
3776H -23-- ' C-1578 the destructive action of fungi. The formation of.
slime by microorganisms in the water from cooling towers can be minimized with the present invention, thus avoiding the deterioration, corrosion, fouling and decreased efficiency of the cooling system which would otherwise result. The large economic losses encountered in pulping and papermaking operations caused by the accumulation of bacterial and fungal slimes in various parts of the system can be eliminated to a significant extent by use of the synergistic admixtures described herein.
The antimicrobial methods of treatment of the present invention involve contacting the microorganisms involved with the synergistic antimicrobial admixtures. This can be accomplished .either by simple addition of the two or more components of the combination together as a single composition, or by addition of the two or moss components separately. Such separate co-administration can either be at the same time or at different times. The net effect will be the same: the article or system being treated will ultimately have incorporated therein or have applied thereto the desired dosage concentration of each component.
In the treatment of aqueous systems, such as cooling water systems, paper and pulp mi~.l~syetems, pools, ponds, lagoons, lakes, etc., to control the growth and/or propagation formation of microorganisms the two components of the combination may be added together as a single compbsition~at orie or at multiple points in the system, or may be added separately, at the same or at different points and/or times of, introduction, thus resulting in the desired antimicrobial effect.
The antimicrobial activity of the synergistic antimicrobial admixtures and individual components thereof described above has been confirmed using standard laboratory techniques. They have been found to be effective, for example, in inhibiting bacteria including ~lebsiella uneumon~ae pneumoniae, Pseudomonas aeruginosa, and I~icrococcus sp. They 1o should also be effective against other bacteria and fungi including Penicilli~m species, ~accharomtCes species, including ~. cerevisiae, Candida species;
Fusarium species, Asnergillus species, and Cenhalospo~y'm species. Such bacteria and/or fungi 15 commonly axe found on cereal and grain products, in ' clay and pigment slurries, in oils, on fruits and vegetables and on cosmetics, leather, electrical insulation, textiles and numerous other materials capable of supporting their growth. Also, such 20 bacteria and/or fungi may be found on plants, seeds, fur and wood and in soils. Further, they may be used to control overgrowth of algae such as rhlor ~~a sp.
including ~. ,pyrenoidosa.
As noted above, it is expected that growth of 25 various harmful fungi and bacteria existing in soil can be eliminated or limited by use of formulations containing the synergistic antimicrobial admixtures described herein. The term ~~sai~.~~ as used here is intended to include all media capable of supporting 3o growth of plants and may include humus, sand, manure, compost, artificially created plant growth solutions and the like.
., The synergistic antimicrobial admixtures described above~have activity against bacteria, yeast, mold, and/or algae when employed at appropriate levels of concentration and may be used to inhibit growth of these organisms. It will be obvious to those skilled in the art that the reguired effective concentration'will var with y particular organisms and in particular applications. In general, however, effective fungicidal, bactericidal and algicidal response is obtained then when the synergistic antimicrobial admixture is employed in 1o concentrations ranging between 1 and 200 ppm (parts per million), preferably 1 and 50 ppm, of polyether phosphonate; and between 1 and 1000 ppm, preferably 1 to 880 ppm, of non-oxidizing biocide, and in a weight ratio of polyether phosphonate/non-oxidizing biocide 15 (on an active basis) of.10:1 to 1:5, preferably 5:1 to 1:3, and even more preferably 3:1 to 1:2. Such levels may be achieved by the administration of the two components of the admixture together as a single composition (optionally comprising other 2o antimicrobial materials and/or inert carriers and excipients), or separately at the same or different points and/or times of introduction.
For other applications of the type described above, amounts of from 0.005 to 1.0% by weight, based 25 on weight of the substrate being treated, of the synergistic antimicrabial combination of the present invention is incorporated into, spxayed onto, used to dip, or otherwise applied to the substrate to be treated in order to prevent growth of bacteria, fungi 30 (including yeasts and molds) and algae.
l ~~~ n Of course, the precise dosages of the components which will be employed depends upon a number of factors. First, the dosage is indicated in parts per million (ppm), which refers to the concentration of the active ingredient in the environment being treated, for example, the concentration of DGH in a cooling water system. This concentration is based on 1~0% active ingredient for convenience in evaluating and comparing test data. In actual practice, ZO however, various percentages of active ingredient may actually be used, with the balanc.e~of the composition being added comprising conventional excipients such as dispersants, stabilizers, preservatives, co-solvents, diluents, and the like.
The components of the synergistic antimicrobial admixtures of the present invention may be added to an article or system to be treated as separate entities, or as combination. The two components may be combined simply as active ingredients, or may 20 additionally be combined with commonly employed carriers and excipients, as described above.
Altk~ough it is believed that the synergistic activity exhibited by the two components is due to their presence as discrete chemical entities, 25 chemical reaction between the two and the formation of adducts or cross-reaction products ie possible.
Such additional active species are also encompassed within the scope of the instant invention.
The following examples will serve to further 30 illustrate the present invention but should not be construed in any Way as being a limitation on the scope thereof .
3776iI -27- C-1578 EXAMPLES OF P FFFRRF J~j~$OpIpj~jvjT, Two series of experiments were set up which consisted of 50 ml solutions of deionized water adjusted to pH 9 with sodium hydroxide. A~.1 the experimental solutions were inoculated witkt a mixed environmental bacteria, cagped and held at ambient room temperature. The first series consisted of a control, containing no biocide, and other solutions each containing a non-oxidizing registered biocide at a typical uee 'concentration. The second series consisted of a second control containing only the tetra methylene phosphonate of Jeffamine*D-230 (JMP), and other solutions each containing a non-oxidizing registered biocide at a typical uee concentration plus 25 mg/L active JMP. At three hours of contaet tame, a one milliliter aliquot was removed from each solution and bacteria bevels Were measured using the standard plate count procedure.
2o This bacterial. measurement was repeated again at 24 hours of contact time. .
percent Bactar~a'~ Kay, 2Q mg/L Didecyl 20 mg/1. Didecyl Dimethyl Ammonium Dimethyl Ammonium Chloride and Chlor d~ 25 ma/~",JMP
3 Houre Kill ~ 90% 99%
24 Hours Kill 83% . 89%
377s~z -28- ~-1578 Example 2:
12.8 mg/L
12.8 mg/L Dodecylguanidine Dodecylguanidine hydrochloride and Hy,~rochloride 25 mall ~P
3 Hours Kill g0% 9g%
24 Hours Kill 67% 89%
dam 1~ a 3:
7.5 mg/L Methylene 7.5 mg/Z Methylene Bisthiocyanate Bisthioc;,canate and 25 mg./L JMP
3 Hours Kill 70% 93%
24 Hours Kill 17% 8g%
gprcent Bacterial Kill 3.75 mg/L
3.75 mg/L 2,2-Dibromo-3-N~r~lo-Prop;ona<m~de and 25 ma/L SIP
3 Hours Kill 90% 99%
24 Hours Kill 0% 89%
Percent Bact ia1 xill 15 mg/I. 15 mg/Ir 2-2-(Thiocyano . (Thiocyano Methylthio) Methylthio) Benzothiazole/ Benzothiazole/
Methylene Bisthiocyanate Bisthiocvanate and 25 me/L 3MP
3 Hours Kill 6s% 99%
24 Hours Kill 0% 83,°g Gontro~ Ba t r;p~'jLevel_s Control ~~l Control #2 ~Io Additives 25 mg_/L ,'(~P
3 Hours Count 250,000 3,500,000 24 Hours Couaat 30,000 175,000 Following the procedures described above, but at pH 7.0, the results set out below were obtained.
~c~iij~i a 7 Percent 3acterial Kill 27 mglT. 25 mg/L 35 mgll.
glutara~dehyd~ Potassium 5-chloro-2-methyl-Dimethyl- 4-isothiazolin-3-d;thioca b mate one and 2-methyl-4-isoth~aio~~.n-3-one 3 Hours Kill 64% 37% 39~
40 mg/L 59 mg/I.
tetrahydro-3- 1,2-dibramo-2,4-5-dimethyl-2-,H-1, r~~.~a~obutane 3, 5-thiadiazin-2~
1 S Glaione 3 Hours Kill 53Z 39%
a
Claims (6)
1. A synergistic antimicrobial admixture comprising an antimicrobially effective amount of:
(A) a polyether polyamino methylene phosphonate compound selected from those of the following formula :
and the N-oxides thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable canon; and each R may be the same or different and is independently selected from hydrogen and methyl; AND
(B) one or more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
(A) a polyether polyamino methylene phosphonate compound selected from those of the following formula :
and the N-oxides thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable canon; and each R may be the same or different and is independently selected from hydrogen and methyl; AND
(B) one or more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole.
2. An admixture according to Claim 1 wherein for component (A), in the above formula, M is hydrogen, R
is methyl, and n is on average about 2.6.
2-(thiocyanomethylthio)benzothiazole.
2. An admixture according to Claim 1 wherein for component (A), in the above formula, M is hydrogen, R
is methyl, and n is on average about 2.6.
3. A method of inhibiting microbial growth, comprising contacting the microbial growth with an antimicrobially effective amount of an admixture comprising:
(A) a polyether polyamino methylene phosphonate compound selected from those of the following formula :
the N-oxides thereof and mixtures thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable cation; and each R may be the same or different and is independently selected from hydrogen and methyl; AND
(B) one or more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane.
(A) a polyether polyamino methylene phosphonate compound selected from those of the following formula :
the N-oxides thereof and mixtures thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable cation; and each R may be the same or different and is independently selected from hydrogen and methyl; AND
(B) one or more members selected from the group consisting essentially of the following non-oxidizing biocides:
didecyl dimethyl ammonium chloride;
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane.
4. A method according to Claim 3 wherein for component (A), in the above formula, M is hydrogen, R
is methyl, and n is on average about 2.6.
is methyl, and n is on average about 2.6.
5. A method of inhibiting the formation, deposition and adherence of scale-forming salts in an aqueous system, while at the same time inhibiting microbial growth in said system, comprising the step of adding to said system an amount sufficient to establish a concentration of from 1 to 100 mg/L of an admixture of a polyether polyamino methylene phosphonate of the following formula:
(A) a polyether polyamino methylene phosphonate compound selected from those of the following formula :
the N-oxides thereof and mixtures thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable cation; and each R may be the same or different and is independently selected from hydrogen and methyl; AND
(B) one or more members selected from the group consisting essentially of the following non-oxidizing, biocides:
didecyl dimethyl ammonium chloride;~
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane.
(A) a polyether polyamino methylene phosphonate compound selected from those of the following formula :
the N-oxides thereof and mixtures thereof; where n is an integer or fractional integer which is, or on average is, from about 2 to about 12, inclusive; M is hydrogen or a suitable cation; and each R may be the same or different and is independently selected from hydrogen and methyl; AND
(B) one or more members selected from the group consisting essentially of the following non-oxidizing, biocides:
didecyl dimethyl ammonium chloride;~
dodecylguanidine hydrochloride;
methylene bisthiocyanate;
2,2-dibromo-3-nitrilo-propionamide;
2-(thiocyanomethylthio)benzothiazole tetrahydro-3,5-dimethyl-2,H-1,3, 5-thiadiazin-2-thione;
1,2-dibromo-2,4-dicyanobutane.
6. A method according to Claim 5 wherein for component (A), in the above formula, M is hydrogen, R
is methyl, and n is on average about 2.6.
is methyl, and n is on average about 2.6.
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US07/961,578 US5457083A (en) | 1992-10-15 | 1992-10-15 | Synergistic antimicrobial combination of polyether phosphonates and non-oxidizing biocides |
US961,578 | 1992-10-15 |
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US3833731A (en) * | 1970-12-28 | 1974-09-03 | Merck & Co Inc | Dihalomethylglutaronitriles used as antibacterial and antifungal agents |
US3873597A (en) * | 1971-04-05 | 1975-03-25 | Merck & Co Inc | 2-Bromo-2-bromomethylglutaronitrile |
GB1460279A (en) * | 1973-05-10 | 1976-12-31 | Ici Ltd | Biocidal compositions |
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US4655815A (en) * | 1985-03-27 | 1987-04-07 | Calgon Corporation | Admixtures of 2-bromo-2-bromomethylglutaronitrile and a formaldehyde donor |
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US4661503A (en) * | 1986-06-16 | 1987-04-28 | Nalco Chemical Company | Synergistic biocide of dodecyl guanidine hydrochloride and a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one |
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US4931189A (en) * | 1988-11-02 | 1990-06-05 | Petrolite Corporation | Methods for inhibition of scale in high brine environments |
JPH0341009A (en) * | 1989-07-07 | 1991-02-21 | Hakutou Kagaku Kk | Germicide composition |
US5041463A (en) * | 1990-08-13 | 1991-08-20 | Betz Laboratories, Inc. | Biocidal compositions and use thereof containing a synergistic mixture of glutaraldehyde and dodecylguanidine hydrochloride |
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1992
- 1992-10-15 US US07/961,578 patent/US5457083A/en not_active Expired - Lifetime
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1993
- 1993-10-12 CA CA002108183A patent/CA2108183C/en not_active Expired - Fee Related
- 1993-10-12 AU AU48983/93A patent/AU658535B2/en not_active Ceased
- 1993-10-12 DE DE69322363T patent/DE69322363T2/en not_active Expired - Fee Related
- 1993-10-12 EP EP93308101A patent/EP0593250B1/en not_active Expired - Lifetime
- 1993-10-14 MX MX9306408A patent/MX9306408A/en unknown
- 1993-10-15 JP JP28170093A patent/JP3487883B2/en not_active Expired - Fee Related
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DE69322363T2 (en) | 1999-04-29 |
JPH0769821A (en) | 1995-03-14 |
AU658535B2 (en) | 1995-04-13 |
EP0593250A1 (en) | 1994-04-20 |
MX9306408A (en) | 1994-04-29 |
AU4898393A (en) | 1994-04-28 |
JP3487883B2 (en) | 2004-01-19 |
CA2108183A1 (en) | 1994-04-16 |
US5457083A (en) | 1995-10-10 |
EP0593250B1 (en) | 1998-12-02 |
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